Dextromethorphan mitigates phantom pain in cancer amputees

Background: Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors may play a role in the persistence of phantom pain. Dextromethorphan (DM) blocks NMDA receptors. Methods: Eight cancer and two noncancer amputees with established, disabling phantom pain received oral DM 60 or 90 mg twice daily (BID) in a three-period double-blind crossover placebo-controlled trial. This followed an open-phase trial in which either dose was given three times daily if pain relief during the double-blind phase was <50% of pretreatment intensity. Patients then underwent a 3-month phase of treatment with the best regimen and a subsequent 1-month posttreatment follow-up. Results: All patients reported a >50% decrease in pain intensity, better mood, and lower sedation in each treatment phase. Four individuals reported this level of pain relief with the 60-mg and one with the 90-mg BID regimen during the double-blind phase, whereas two amputees benefited from the 60-mg and three from the 90-mg thrice-daily regimen in the open-phase trial. One reported exacerbation of pain with the 90-mg BID regimen, and three reported pain rebound at the 1-month posttreatment follow-up phase. Three patients stopped all previous analgesic use during the study. Conclusions: Persistent phantom pain probably involves NMDA receptor hyperexcitability because DM 120 to 270 mg/day mitigated the pain satisfactorily.